Gene Therapy Protocols pp 133-160
PEGylated Adenovirus for Targeted Gene Therapy
Bifunctional polyethylene glycol (PEG) molecules provide a novel approach to retargeting viral vectors without the need to genetically modify the vector. Modification of the surface of adenovirus with heterofunctional PEG allows further modification of the capsid with ligands. In addition, heterofunctional PEG modification ablates the normal tropism of the virus and reduces transduction of non-target tissues in vivo. Moreover, the addition of PEG chains to the surface of the virus shields antigen-binding sites, significantly reducing the susceptibility of the virus to antibody neutralization. Finally, T cell subsets from mice exposed to the PEGylated vector demonstrate a marked decrease in Th1 and Th2 responses, suggesting that PEG modification may help reduce the immune response to the vector.